自身免疫性肝炎、原发性胆汁性胆管炎及其重叠综合征患者外周血OX40/OX40L的表达及意义

王维钊; 朱沁玲; 向晓星; 马莉; 顾达; 童聪; 王婷婷; 何家俊; 刘军; 王璐; 陈超伍

doi:10.3969/j.issn.1001-5256.2020.12.020

自身免疫性肝炎、原发性胆汁性胆管炎及其重叠综合征患者外周血OX40/OX40L的表达及意义

DOI: 10.3969/j.issn.1001-5256.2020.12.020

1. 江苏省苏北人民医院扬州大学临床医学院内镜诊治中心
2. 江苏省苏北人民医院扬州大学临床医学院消化内科
3. 大连医科大学研究生院
4. 江苏省苏北人民医院扬州大学临床医学院风湿免疫检测中心

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出版历程
- 收稿日期: 2020-06-10
- 出版日期: 2020-12-20

Expression and significance of OX40/OX40L in peripheral blood of patients with autoimmune hepatitis,primary biliary cholangitis,and their overlap syndrome

Center of Endoscopic Diagnosis and Treatment,Subei People's Hospital of Jiangsu & Clinical Medical College of Yangzhou University
Department of Gastroenterology,Subei People's Hospital of Jiangsu & Clinical Medical College of Yangzhou University
Graduate School,Dalian Medical University
Center of Rheumatology and Immunology,Subei People's Hospital of Jiangsu & Clinical Medical College of Yangzhou University

摘要

摘要:
目的探讨自身免疫性肝炎（AIH）、原发性胆汁性胆管炎（PBC）及其重叠综合征患者经规范化治疗前后外周血中OX40/OX40L（CD134/CD134L）在CD4+T淋巴细胞、CD8+T淋巴细胞、单核细胞、B淋巴细胞的表达情况及其临床意义。方法选取2015年8月-2019年8月在江苏省苏北人民医院就诊的74例确诊AIH、PBC及其重叠综合征患者,按照相关诊断标准分为AIH组（29例）、PBC组（26例）、重叠综合征组（19例）（即A、P、C组）,同时设置健康对照30例。在规范化治疗前后抽取患者外周血标本,采用免疫荧光标记流式细胞术检测OX40/OX40L在外周血细胞表面的表达情况,比较OX40/OX40L在治疗前后、健康对照组的表达差异。多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验,配对样本两组间比较采用配对t检验。结果 3组在性别年龄构成上差异均无统计学意义（P值均> 0. 05）。治疗前:A、P、C 3组外周血中CD4+T淋巴细胞的OX40阳性率依次升高,且均高于对照组,依次为:（14. 80±4. 99）%、（17. 11±2. 71）%、（25. 18±5...
- 自身免疫性肝炎 /
- 原发性胆汁性胆管炎 /
- 重叠综合征 /
- 受体,OX40 /
- OX40配体
Abstract:
Objective To investigate the expression and clinical significance of OX40/OX40 L( CD134/CD134 L) in CD4 + T cells,CD8 +T cells,monocytes,and B lymphocytes in peripheral blood of patients with autoimmune hepatitis( AIH),primary biliary cholangitis( PBC),and their overlap syndrome before and after standardized treatment. Methods A total of 74 patients with AIH,PBC,and their o-verlap syndrome who were diagnosed in Subei People's Hospital of Jiangsu from August 2015 to August 2019 were enrolled,and according to related diagnostic criteria,they were divided into AIH group( group A) with 29 patients,PBC group( group P) with 26 patients,and overlap syndrome group( group C) with 19 patients. A healthy control group with 30 individuals was also established. Peripheral blood samples were collected before and after standardized treatment to measure the expression of OX40/OX40 L on the surface of peripheral blood cells by immunofluorescence flow cytometry,and the expression of OX40/OX40 L was compared before and after treatment and between the three groups and the healthy control group to investigate its clinical significance. A one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups; the paired t-test was used for comparison of paired samples between two groups. Results There were no significant differences in sex composition and age composition between the three groups( P > 0. 05). Before treatment,the positive rate of OX40 in peripheral blood CD4+T cells gradually increased in groups A,P,and C,and groups A,P,and C had a significantly higher positive rate of OX40 than the control group( 14. 80% ± 4. 99%/17. 11% ± 2. 71%/25. 18% ± 5. 55% vs 6. 67% ± 2. 26%,F = 14. 823,P < 0. 001); groups A,P,and C had a significantly higher positive rate of OX40 in CD8+T cells than the control group( 4. 86% ± 1. 54%/6. 40% ± 1. 88%/7. 33% ± 2. 12% vs 4. 09% ± 2. 69%,F =5. 486,P < 0. 001); the positive rate of OX40 L in CD14+monocytes was 19. 84% ± 6. 11% in group A,21. 17% ± 4. 35% in group P,29. 13% ± 6. 32% in group C,and 4. 86% ± 2. 34% in the control group,and there was a significant difference between groups( F =17. 004,P < 0. 001); the positive rate of OX40 L in CD19+B cells was 17. 62% ± 3. 86% in group A,14. 75% ± 4. 32% in group P,10. 13% ± 2. 56% in group C,and 4. 50% ± 1. 38% in the control group,showing a trend of gradual reduction,and groups A,P,and C had a significantly higher positive rate than the control group( F = 12. 221,P < 0. 001). After treatment,the positive rate of OX40 in CD8+T cells decreased significantly to a similar level as the control group,and there was no significant difference between groups( F =0. 731,P = 0. 538). For the other three types of cells,although there were varying degrees of reduction in the positive rate of OX40/OX40 L after treatment,groups A,P,and C still had a significantly higher positive rate than the control group; in CD4+T cells,the positive rate of OX40 was 11. 00% ± 1. 98% in group A,13. 72% ± 1. 03% in group P,19. 72% ± 3. 47% in group C,and 6. 67% ± 2. 26% in the control group,and groups A,P,and C had a significantly higher positive rate than the control group( F = 11. 365,P < 0. 001); in CD14+monocytes,the positive rate of OX40 L was 11. 82% ± 2. 23% in group A,15. 19% ± 4. 42% in group P,24. 51% ± 4. 09% in group C,and 4. 86% ± 2. 34% in the control group,and groups A,P,and C had a significantly higher positive rate than the control group( F =13. 748,P < 0. 001); in CD19+B cells,the positive rate of OX40 L was 9. 09% ± 3. 25% in group A,6. 81% ± 2. 20% in group P,7. 48% ± 2. 85% in group C,and 4. 50% ± 1. 38% in the control group,and groups A,P,and C had a significantly higher positive rate than the control group( F = 8. 052,P < 0. 001). Groups A,P,and C had significant reductions in the expression of OX40/OX40 L in peripheral blood CD4+T cells,CD8+T cells,CD14+monocytes,and CD19+B lymphocytes after treatment( all P < 0. 05). Conclusion The expression of OX40/OX40 L in peripheral blood increases in patients with AIH,PBC,and their overlap syndrome and decreases after treatment,indicating that the OX40/OX40 L pathway is involved in the pathogenesis of the above diseases,and the role of OX40 on the surface of CD8+T cells may better reflect the treatment outcome.
- hepatitis,autoimmune /
- primary biliary cholangitis /
- overlap syndrome /
- receptors,OX40 /
- OX40 ligand

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